Inaki Etxeberria, PhD, CRI Postdoctoral Fellow Memorial Sloan Kettering Cancer Center Area of Research: Colorectal Cancer, Melanoma Dr. Inaki Etxeberria is investigating strategies to target immunotherapy-resistant cancers that express a mutated version of an important growth-promoting gene. Although some patients experience long-lasting benefit with current cancer immunotherapies, many fail to respond or end up progressing after initially responding. More than 25% of melanomas, as well as some colorectal cancers, harbor mutated versions of NRAS, a growth-related pathway that can drive cancer progression. Patients with mutated NRAS are less likely to respond to immunotherapy, and therefore new therapies are urgently needed for people with these cancers. A major gap in knowledge that is limiting NRAS-based immunotherapy approaches is the need to identify immune-stimulating targets that are selectively expressed only by tumor cells.Recently, Dr. Exteberria discovered that NRAS mutations generate markers known as neo-antigens that are expressed exclusively by the tumor cells, and now he’s working to develop T cell receptor (TCR)-based immunotherapies to target these cancers with mutated NRAS. Using a unique collection of samples from patients whose tumors express mutated NRAS, he has generated T cells specific for this mutation and confirmed their ability to effectively target the cancer cells. Moving forward he’s focused on optimizing this cell therapy approach to target melanoma and other common cancers with genetic features linked to immunotherapy resistance. Overall, these studies should generate new generalizable knowledge that improves our understanding of how the adaptive immune system can distinguish between normal and cancerous tissues. Projects and Grants Immunogenic landscape and therapeutic targeting of NRAS “public” neoantigens Memorial Sloan Kettering Cancer Center | Melanoma, Colorectal cancer | 2023 | Christopher Klebanoff, MD
